RÉSUMÉ
BACKGROUND: The purpose of our study was to evaluate the usefulness of hip arthroscopy including extensive capsulectomy for synovial chondromatosis of the hip. METHODS: From 2008 to 2016, 13 patients with synovial chondromatosis of the hip were treated with arthroscopic removal of loose bodies and synovectomy using three arthroscopic portals. An extensive capsulectomy was performed to allow the remaining loose bodies to be out of the extracapsular space, and the excised capsule was not repaired. All patients were assessed by clinical scores and the radiographs were reviewed to determine whether the remaining loose bodies disappeared at the last follow-up. RESULTS: Eight men and two women were followed up for a minimum of 1 year (mean, 3.8 years; range, 1 to 6.8 years) after hip arthroscopy. Clinical outcomes such as modified Harris hip score, University of California Los Angeles score, and Western Ontario and McMaster Universities Osteoarthritis Index score improved at the last follow-up. Although seven hips had remaining loose bodies after arthroscopic surgery, the remaining loose bodies disappeared in five hips (71.4%) at the last follow-up. CONCLUSIONS: Arthroscopic surgery was useful to treat synovial chondromatosis of the hip. In spite of limited removal of loose bodies, arthroscopic procedures including extensive capsulectomy could be effective for the treatment of synovial chondromatosis of the hip.
Sujet(s)
Arthroscopie , Chondromatose synoviale/chirurgie , Articulation de la hanche/chirurgie , Arthrophytes/chirurgie , Adulte , Arthroscopie/effets indésirables , Arthroscopie/méthodes , Arthroscopie/statistiques et données numériques , Chondromatose synoviale/imagerie diagnostique , Femelle , Articulation de la hanche/imagerie diagnostique , Humains , Arthrophytes/imagerie diagnostique , Mâle , Adulte d'âge moyen , Études rétrospectives , Synovectomie/effets indésirables , Synovectomie/méthodes , Synovectomie/statistiques et données numériques , Résultat thérapeutique , Jeune adulteRÉSUMÉ
BACKGROUND: Medial opening wedge high tibial osteotomy (HTO) entails extensive soft tissue release that may lead to substantial perioperative bleeding. Although tranexamic acid (TXA) is a well-established blood-conserving agent in total joint arthroplasty, its potential to reduce blood loss in patients undergoing HTO has not been studied extensively. QUESTIONS/PURPOSES: (1) Does TXA reduce total estimated blood loss in HTO? (2) Does TXA use in HTO affect in-hospital endpoints as measured by visual analog scale (VAS) pain scores at rest the day after surgery, wound complications in the immediate postoperative period, blood transfusions, or symptomatic deep vein thrombosis? METHODS: Between January 2015 and May 2017, a single surgeon performed 156 HTOs, all of which were done using the medial opening wedge technique. We began using intravenous TXA for all HTOs in June 2016. This left us with 89 patients who were treated during a time when no TXA was used and 67 patients who were treated when all patients received TXA. Two patients in the control group had simultaneous TKA in the contralateral leg and one patient in each group had missing data so these patients were excluded, leaving 86 (97%) patients in the control group and 66 (98.5%) in the TXA group available for analysis in this retrospective study. There were no demographic differences between the groups in terms of age, sex, body mass index, and baseline hemoglobin values. Total estimated blood loss was the primary outcome variable, which was calculated using total blood volume and decrease in hemoglobin values. Secondary outcome variables included pain VAS at rest the day after surgery, wound complications in the immediate postoperative period, allogeneic blood transfusions, and occurrence of symptomatic thromboembolic manifestations. The decision on when to transfuse was based on predetermined criteria. An orthopaedic surgeon not involved in patient care collected the patient data from electronic medical records and did chart review. RESULTS: The TXA group had less total blood loss (372 ± 36 mL versus 635 ± 53 mL, mean difference 263 mL [95% confidence interval, 248-278]; p < 0.001). Between groups, differences in VAS pain scores at rest the day after surgery favored the TXA group but were small and unlikely to be clinically important. There were two wound complications in the control group (one hematoma and one superficial wound infection) and none in the TXA group. No patients in either group received a blood transfusion, and no symptomatic thromboembolic events were detected in either group. CONCLUSIONS: This study demonstrates that the systemic administration of TXA reduces postoperative blood loss in medial opening wedge HTO; however, insofar as no transfusions were administered to patients even before the routine use of TXA in this series, and no clinically important differences in pain scores were identified, the clinical benefit of routine use of TXA in patients undergoing HTO is uncertain. Our study was too small to make safety-related claims on rare endpoints such as wound complications or thromboembolic events. Larger, and preferably randomized, trials are needed to help define whether it is important to use TXA in this setting. Our data can help inform sample size calculations for such studies. LEVEL OF EVIDENCE: Level III, therapeutic study.
Sujet(s)
Antifibrinolytiques/administration et posologie , Ostéotomie/méthodes , Hémorragie postopératoire/prévention et contrôle , Tibia/chirurgie , Acide tranéxamique/administration et posologie , Adulte , Antifibrinolytiques/effets indésirables , Transfusion sanguine , Femelle , Humains , Perfusions veineuses , Mâle , Adulte d'âge moyen , Ostéotomie/effets indésirables , Douleur postopératoire/étiologie , Hémorragie postopératoire/étiologie , Études rétrospectives , Facteurs de risque , Thromboembolie/étiologie , Facteurs temps , Acide tranéxamique/effets indésirables , Résultat thérapeutique , Thrombose veineuse/étiologie , Cicatrisation de plaieRÉSUMÉ
PURPOSE: To compare the clinical and radiologic outcomes of chronically retracted rotator cuff tears by arthroscopic medializing and non-medializing repair (restoring anatomic footprint and performing conventional repair). METHODS: This study retrospectively reviewed 195 patients who underwent arthroscopic double-row modified Mason-Allen repair for large, full-thickness rotator cuff tears from January 2013 to July 2015. We included a total of 60 of these patients and divided them into 2 groups: those who underwent medialization (n = 24) and those who did not (n = 36). Magnetic resonance imaging was performed at a minimum of 6 months (mean, 15.2 months; range, 6-24 months) postoperatively to assess cuff integrity. Patients were clinically evaluated at least 1 year postoperatively (mean, 18.9 months; range, 12-60 months) with a visual analog scale, the American Shoulder and Elbow Surgeons score, the University of California-Los Angeles Shoulder Rating Scale score, and the Constant score. RESULTS: The mean medialization length was 10.5 mm (range, 6.5-15.6 mm) on magnetic resonance imaging. The retear rate was 8.3% (n = 2) in the medialization group and 31% (n = 11) in the non-medialization group (P = .041). At last follow-up, the mean visual analog scale, American Shoulder and Elbow Surgeons, University of California-Los Angeles, and Constant scores improved significantly from 5.3 ± 1.4, 38.5 ± 8.8, 22.5 ± 3.1, and 41.7 ± 9.9, respectively, to 1.8 ± 1.1, 85.3 ± 7.5, 31.8 ± 2.5, and 90.2 ± 6.9, respectively, with medialization and from 4.0 ± 1.6, 51.5 ± 10.5, 20.0 ± 3.9, and 55.9 ± 10.5, respectively, to 1.4 ± 1.0, 88.6 ± 9.0, 31.0 ± 9.3, and 89.4 ± 9.3, respectively, with non-medialization (P < .001), although there were no significant differences between the groups (P = .165, P = .653, P = .250, and P = .113, respectively). CONCLUSIONS: Medialization of approximately 10.5 mm reliably shows good clinical results, and medializing rotator cuff tendons should be considered as a treatment option for repairing rotator cuff tears with chronic retracted tendons. LEVEL OF EVIDENCE: Level III, retrospective comparative study.
Sujet(s)
Lésions de la coiffe des rotateurs/chirurgie , Coiffe des rotateurs/chirurgie , Tendons/chirurgie , Adulte , Sujet âgé , Arthroscopie/méthodes , Maladie chronique , Femelle , Humains , Imagerie par résonance magnétique/méthodes , Mâle , Adulte d'âge moyen , Études rétrospectives , Coiffe des rotateurs/imagerie diagnostique , Lésions de la coiffe des rotateurs/imagerie diagnostique , Lésions de l'épaule , Articulation glénohumérale/imagerie diagnostique , Articulation glénohumérale/chirurgie , Résultat thérapeutique , Échelle visuelle analogiqueRÉSUMÉ
BACKGROUND: The purpose of this study was to determine whether there is a learning curve for internal fixation for nondisplaced femoral neck fractures using the cumulative sum (CUSUM) technique. We applied the CUSUM technique in monitoring performance of a single surgeon in internal fixation for nondisplaced femoral neck fractures. METHODS: Fifty consecutive patients who underwent internal fixation for nondisplaced femoral neck fractures were evaluated retrospectively. Loss of fixation within 6 months postoperatively was considered as failure of treatment. Patients were stratified into the early experience group (cases 1 to 25) and the late experience group (cases 26 to 50). The CUSUM method was used to analyze the learning curve. RESULTS: There was no failure of treatment during study period. The operation time became shorter with experience. Using the CUSUM analysis to plot the learning curve, there was no significant learning curve observed for multiple pinning for nondisplaced femoral neck fractures. CONCLUSIONS: The CUSUM analysis revealed there was no obvious learning curve to become proficient at internal fixation for nondisplaced femoral neck fractures, if technical principles were followed during the procedure.
Sujet(s)
Fractures du col fémoral/chirurgie , Ostéosynthèse interne/méthodes , Courbe d'apprentissage , Sujet âgé , Sujet âgé de 80 ans ou plus , Clous orthopédiques , Femelle , Ostéosynthèse interne/instrumentation , Humains , Mâle , Adulte d'âge moyen , Durée opératoire , Études rétrospectives , Facteurs temps , Échec thérapeutiqueRÉSUMÉ
BACKGROUND: The incidence of hip fractures has been reported to vary geographically, and its trend has also varied widely. However, the trend in the age-adjusted incidence of hip fractures has not been well studied in Korea. After we identified eligible studies presenting multiple age-adjusted incidences of hip fractures in the Korean population in PubMed, we evaluated changes in the absolute number of occurrence and calculated the annual percentage change (APC) of age-adjusted incidences of hip fractures. METHODS: We have searched PubMed for the original and English-language literature on the incidence of hip fractures in the Korean population published since 2000. The studies presenting multiple age-adjusted incidences of hip fractures were selected. We evaluated the change in the absolute number of hip fractures and calculated the APC of age-adjusted incidences of hip fractures for each study. RESULTS: Three eligible articles were identified. The absolute number of hip fractures for both genders increased over time in all three studies although the operational definition of hip fracture differed from one another. The APC of the age-adjusted incidence of hip fractures was positive for women and negative for men. However, the change was not statistically significant in both genders during each study period (2001-2004, 2005-2008, and 2006-2010, respectively). CONCLUSIONS: The age-adjusted incidence of hip fractures was stable among men and women, while the absolute number of hip fractures increased for both genders in Korea. Further studies with longer study periods on age-adjusted incidences are required to better determine the trend in the incidence of hip fractures in Korea.
Sujet(s)
Fractures de la hanche/épidémiologie , Facteurs âges , Humains , Incidence , République de Corée/épidémiologie , Facteurs sexuelsRÉSUMÉ
Since insulin sensitivity to cells is attributed to phosphorylation of the insulin receptor (IR), protein tyrosine phosphatase 1B (PTP1B), which dephosphorylates the tyrosine residues of IR proteins, is primarily responsible for insulin resistance in type 2 diabetes. Therefore, PTP1B inhibitors ameliorating the insulin-dependent signaling pathway are potential therapeutic candidates for the treatment and prevention of diabetes. As part of our continuous search for diterpenes derived from Aralia continentalis as potent PTP1B inhibitors, five active diterpenoids, including ent-pimara-8(14),15-diene-19-oic acid (1); 7-oxo-ent-pimara-8(14),15-diene-19-oic acid (2); 7ß-hydroxy-ent-pimara-8(14),15-diene-19-oic acid (3); ent-pimara-8(14),15-diene-19-ol (4); 8α-hydroxy-ent-pimara-15-en-19-ol (5); and ent-kaur-16-en-19-oic-acid (6) were investigated using the enzyme kinetic assay. With the exception of 1 showing mixed inhibition, compounds 2 and 4-6 exhibited noncompetitive inhibition against PTP1B with K i values ranging 3.29-12.86 µM. In particular, 2 with an oxo group in the C-7 position showed increased PTP1B inhibition compared to nonsubstituted 1. Based on the structure and activity relationship, the 3D docking simulations of 1, 2, and 3 were also performed. Compounds 1-3 showed negative binding energies of -5.3 to -6.1 kcal/mol and a high affinity to PTP1B residues (Phe182 and Asp181 in the WPD loop; Cys215 in the active sites; Tyr46, Arg47, Asp48, Val49, Ser216, Ala217, Gly218, Ile219, Gly220, Arg221, Gln262, and Gln266 in the pocket site), indicating that they may stabilize the open form and generate tighter binding to the catalytic sites of PTP1B. The enzymatic kinetics and docking results clearly indicate the promising potential of pimarane-type diterpenes as PTP1B inhibitors.
Sujet(s)
Abiétanes/métabolisme , Abiétanes/pharmacologie , Aralia , Racines de plante , Protein Tyrosine Phosphatase, Non-Receptor Type 1/antagonistes et inhibiteurs , Protein Tyrosine Phosphatase, Non-Receptor Type 1/métabolisme , Abiétanes/composition chimique , Sites de fixation/physiologie , HumainsRÉSUMÉ
BACKGROUND CONTEXT: Low-dose aspirin for the prevention of cardiovascular disease is recommended to be discontinued at least 7 days before spinal surgery. PURPOSE: To determine the effect of stopping low-dose aspirin at least 7 days before surgery on the level of the perioperative blood loss or complications related to hemorrhage. STUDY DESIGN: Retrospective case study. PATIENT SAMPLE: Patients who underwent spinal fusion surgery for degenerative lumbar disease. OUTCOME MEASURE: Clinical outcome was measured by the Oswestry Disability Index. METHODS: The aspirin group included 38 patients who had taken 100 mg aspirin for an average of 40.3 months. They stopped aspirin for at least 7 days before surgery (mean, 9.0 days). The control group included 38 patients who had not taken aspirin. Both groups were matched in terms of age, gender, number of fused segments, and surgical procedures. The diagnosis in all patients was degenerative spinal disease. RESULTS: The mean age in the aspirin and control groups was 68.5 and 69.1 years, respectively. The mean number of levels fused was 2.0 segments in both groups. During surgery, the estimated blood loss was 855.3 cc in the aspirin group and 840.8 cc in the control group with no significant difference (p=.84). However, there was a significant difference in blood drainage after surgery. The hemovac blood drainage after surgery was 864.4 cc in the aspirin group but only 458.4 cc in the control group (p<.001). Therefore, the transfusion requirement after surgery was significantly greater in the aspirin group than in the control group (p=.03). The rate of complications related to hemorrhage was higher in the aspirin group than in the control group. CONCLUSIONS: The intraoperative blood loss during spinal fusion surgery was similar in both groups. However, the blood drainage after surgery was significantly higher in the aspirin group despite stopping aspirin 7 days before surgery. Hence, surgeons should pay careful attention to postoperative blood loss and complications related to hemorrhage in patients who have been taking low-dose aspirin.
Sujet(s)
Anti-inflammatoires non stéroïdiens/effets indésirables , Acide acétylsalicylique/effets indésirables , Perte sanguine peropératoire/prévention et contrôle , Hémorragie postopératoire/induit chimiquement , Arthrodèse vertébrale , Sujet âgé , Femelle , Humains , Mâle , Études rétrospectivesRÉSUMÉ
The principal objective of this study was to evaluate the antibacterial activities of macrolactin A (MA) and 7-O-succinyl macrolactin A (SMA) generated from Bacillus polyfermenticus KJS-2 against vancomycin-resistant enterococci (VREs) and methicillin-resistant Staphylococcus aureus. The minimal inhibitory concentrations (MICs) of MA and SMA against VREs were 16 and 2â¼1 µg/mL, respectively, and the MICs of MA and SMA against methicillin-resistant Staphylococcus aureus were 2 and < 0.25 µg/mL, respectively. Their MIC values were comparable or superior to those of teicoplanin. In evaluating the inhibitory effects of intestinal VRE colonization in mice, the oral MA and SMA effected a rapid inhibition of intestinal VRE colonization in mice, and the intraperitoneal SMA also inhibited VRE colonization, whereas intraperitoneal MA did not.
Sujet(s)
Antibactériens/pharmacologie , Bacillus/métabolisme , Macrolides/pharmacologie , Animaux , Antibactériens/isolement et purification , Enterococcus/effets des médicaments et des substances chimiques , Femelle , Intestins/microbiologie , Macrolides/isolement et purification , Staphylococcus aureus résistant à la méticilline/effets des médicaments et des substances chimiques , Souris , Souris de lignée ICR , Tests de sensibilité microbienne , Téicoplanine/pharmacologie , Résistance à la vancomycineRÉSUMÉ
One of the strains of the Bacillus mojavensis group, Bacillus mojavensis KJS-3 (B. mojavensis KJS-3), which has been demonstrated to play a role in protecting plants against diseases as a bacterial endophyte and in reducing the accumulation of mycotoxins generated by an endophytic fungus, was recently discovered in food waste. In this study, the identification and characterization of B. mojavensis KJS-3 was performed via TEM analysis, API-zym test, API 50 CHB test, assays of catalase and oxidase activity, lactic acid production, stability under various conditions, antibiotic susceptibility, and cellular fatty acid composition. The overall results of this study demonstrate that B. mojavensis KJS-3 may have great potential as a probiotic product, as this bacterium is quite stable in somewhat harsh environments. B. mojavensis KJS-3 was positive on oxidase and catalase tests, and the conversion rate of glucose to lactic acid was 58.9%. Finally, anteiso-C(15:0) (43.10%) was identified as the major fatty acid.
Sujet(s)
Bacillus/physiologie , Probiotiques , Bacillus/composition chimique , Bacillus/cytologie , Bacillus/isolement et purification , Catalase/métabolisme , Stabilité de médicament , Tomographie en microscopie électronique , Acides gras/analyse , Acide lactique/biosynthèse , Tests de sensibilité microbienne , Oxidoreductases/métabolisme , Probiotiques/isolement et purificationRÉSUMÉ
This article describes the treatment of a bony mallet finger deformity using 2 extension-block Kirschner wires (K-wires) with a transarticular K-wire fixation technique for precise alignment of the terminal extensor tendon-bone relationship and effective immobilization of the distal interphalangeal joint. Twenty-nine patients (33 fingers) with a bony mallet finger deformity and fracture fragment involving more than one-third of the articular surface were treated surgically. The fracture fragment was fixed and the mallet finger deformity was corrected in all patients using modified extension-block K-wires (2 dorsal extension-block pins) with a transarticular K-wire (volar side pin) fixation technique. Active motion of the proximal interphalangeal and metacarpophalangeal joints was not restricted. The wires are removed in the clinic 6 weeks postoperatively when the bridging trabeculae were observed in the radiographs, and immobilization in a stock splint was continued for an additional 2 weeks. According to Crawford's evaluation criteria, there were 24 (73%) excellent, 7 (21%) good, and 2 (6%) fair results. Three patients showed radiological signs of mild degenerative changes, which did not limit their daily activities. Nail ridging occurred in 3 cases (9%), which disappeared after an average of 6 months with normal growth, and mild scarring at the dorsal pin site occurred in 2 cases (6%). Modified extension-block K-wires with a transarticular K-wire fixation technique is an acceptable alternative treatment modality for the management of bony mallet finger deformities with or without subluxation of the distal phalanx.
Sujet(s)
Traumatismes du doigt/chirurgie , Articulation du doigt/chirurgie , Ostéosynthèse interne/méthodes , Anomalies morphologiques acquises de la main/chirurgie , Adolescent , Adulte , Fils métalliques , Femelle , Traumatismes du doigt/imagerie diagnostique , Traumatismes du doigt/physiopathologie , Articulation du doigt/imagerie diagnostique , Articulation du doigt/physiopathologie , Ostéosynthèse interne/instrumentation , Anomalies morphologiques acquises de la main/imagerie diagnostique , Anomalies morphologiques acquises de la main/physiopathologie , Humains , Mâle , Adulte d'âge moyen , Radiographie , Amplitude articulaire , Récupération fonctionnelle , Jeune adulteRÉSUMÉ
The full length genes gyrB (2,415 bp), parC (2,277 bp), and parE (1,896 bp) in Edwardsiella tarda were cloned by PCR with degenerate primers based on the sequence of the respective quinolone resistance-determining region (QRDR), followed by elongation of 5' and 3' ends using cassette ligation-mediated PCR (CLMP). Analysis of the cloned genes revealed open reading frames (ORFs) encoding proteins of 804 (GyrB), 758 (ParC), and 631 (ParE) amino acids with conserved gyrase/topoisomerase features and motifs important for enzymatic function. The ORFs were preceded by putative promoters, ribosome binding sites, and inverted repeats with the potential to form cruciform structures for binding of DNA-binding proteins. When comparing the deduced amino acid sequences of E. tarda GyrB, ParC, and ParE with those of the corresponding proteins in other bacteria, they were found to be most closely related to Escherichia coli GyrB (87.6% identity), Klebsiella pneumoniae ParC (78.8% identity) and Salmonella typhimurium ParE (89.5% identity), respectively. The two topoisomerase genes, parC and parE, were found to be contiguous on the E. tarda chromosome. All 18 quinoloneresistant isolates obtained from Korea thus far did not contain subunit alternations apart from a substitution in GyrA (Ser83âArg). However, an alteration in the QRDR of ParC (Ser84âIle) following an amino acid substitution in GyrA (Asp87âGly) was detected in E. tarda mutants selected in vitro at 8 microng/ml ciprofloxacin (CIP). A mutant with a GyrB (Ser464âLeu) and GyrA (Asp87âGly) substitution did not show a significant increase in the minimum inhibitory concentration (MIC) of CIP. None of the in vitro mutants exhibited mutations in parE. Thus, gyrA and parC should be considered to be the primary and secondary targets, respectively, of quinolones in E. tarda.
Sujet(s)
Antibactériens/pharmacologie , DNA gyrase/génétique , DNA topoisomerase IV/génétique , Résistance bactérienne aux médicaments , Edwardsiella tarda/effets des médicaments et des substances chimiques , Quinolinone/pharmacologie , Motifs d'acides aminés , Substitution d'acide aminé/génétique , Clonage moléculaire , ADN bactérien/composition chimique , ADN bactérien/génétique , Edwardsiella tarda/génétique , Corée , Tests de sensibilité microbienne , Données de séquences moléculaires , Analyse de séquence d'ADN , Similitude de séquences d'acides aminésRÉSUMÉ
Previous studies on the anticonvulsant activity of N-Cbz-alpha-aminoglutarimides have shown that the derivatives of N-Cbz-alpha-amino-N-alkoxy glutarimide have significant anticonvulsant activity. In addition, their anticonvulsant activities are dependent on the presence of N-alkoxy groups. Based on these results, a series of N-Cbz-alpha-amino-glutarimidooxy carboxylates derivatives (3a-e) were synthesized in moderate yield using a known synthetic procedure. Their anticonvulsant activities were evaluated using the maximal electroshock seizure (MES) test, the pentylene tetrazole induced seizure (PTZ) test, and the strychinine (Str) threshold test with the ultimate aim of developing more active anticonvulsants. None of the compounds (3a-e) tested showed anticonvulsant activity in the MES and PTZ test. However, all the compounds tested exhibited significant anticonvulsant activity in the Str. test. The most active compound in the Str. test was the methyl ester of N-Cbz-alpha-amino-glutarimidooxy acetic acid 3a (ED50 = 42.9 mg/kg).
Sujet(s)
Anticonvulsivants/pharmacologie , Acides carboxyliques/pharmacologie , Pipéridones/pharmacologie , Crises épileptiques/prévention et contrôle , Animaux , Anticonvulsivants/synthèse chimique , Acides carboxyliques/synthèse chimique , Mâle , Souris , Souris de lignée ICR , Pipéridones/synthèse chimique , Crises épileptiques/induit chimiquement , Relation structure-activité , StrychnineRÉSUMÉ
In previous studies for the development of new anticonvulsants, we found that N-Cbz-alpha-amino-N-alkylsuccinimides exhibited significant anticonvulsant activities in the Maximal electroshock seizure (MES) and Pentylenetetrazole induced seizure (PTZ) tests, and also their anticonvulsant activities were dependent on the N-alkyl substituents existent in their structures. Based on these estimations, N-Cbz-alpha-amino-N-hydroxysuccinimide and various N-Cbz-alpha-amino-N-alkoxysuccinimides were prepared in order to develop more active anticonvulsants and to examine the effects of N-hydoxy or N-alkoxy groups on their anticonvulsant activities. The (R)- or (S)-N-Cbz-alpha-amino-N-hydroxysuccinimide and N-Cbz-alpha-amino-N-alkoxysuccinimides were prepared from the corresponding (R)- or (S)-N-Cbz-aspartic acid through the known synthetic procedures. Their anticonvulsant activities in the MES and PTZ test were evaluated. All of these compounds except 3a showed significant anticonvulsant activities against the PTZ test, but these compounds were not active in the MES test. The most active compound in the PTZ test was (R)-N-Cbz-alpha-amino-N-benzyloxysuccinimide (ED50=62.5 mg/kg). In addition, the anticonvulsant activities of these compounds were dependent on their N-substited groups. The order of anticonvulsant activity against the PTZ test, as judged from the ED50 values for (R) series was N-benzyloxy > N-hydroxy > N-isopropoxy > N-methoxy > N-ethoxy; for the (S) series N-ethoxy > N-benzyloxy > N-methoxy > N-isopropoxy.
Sujet(s)
Anticonvulsivants/synthèse chimique , Anticonvulsivants/usage thérapeutique , Crises épileptiques/traitement médicamenteux , Succinimides/synthèse chimique , Succinimides/usage thérapeutique , Animaux , Évaluation préclinique de médicament/méthodes , Mâle , Souris , Souris de lignée ICRRÉSUMÉ
In our previous studies for the development of new anticonvulsant of broad spectrum, we found that N-cbz-alpha-aminoglutarimides showed significant anticonvulsant activities of broad spectrum enough to be recommended for the new anticonvulsants and their anticonvulsant activities were dependent on their imide substituent groups. Based on these results, various N-cbz-alpha-amino-N-alkoxyglutarimides, where the imide N-H was substituted with the hydroxy and alkoxy group, were prepared and evaluated for their anticonvulsant activities using the Maximal electroshock seizure (MES) and Pentylenetetrazole induced seizure (PTZ) tests and also the rotorod test. A series of (R) or (S)-N-cbz-alpha-amino-N-alkoxyglutarimides could be prepared from the corresponding (R) or (S)-N-cbz-glutamic acid following the usual synthetic procedure. Among them, (R)-N-cbz-alpha-amino-N-hydroxyglutarimide (ED50=86.25 mg/kg) was most active in the MES test. In the case of the PTZ test, (R)-N-cbz-alpha-amino-N-benzyloxyglutarimide (ED50=62.5 mg/kg) was most active. Among the tested compounds, 2a-c, 3a, and 3b showed anticonvulsant activities in the MES and PTZ test. All of the tested compounds, except 2f and 3f, showed significant anticonvulsant activities in the MES or PTZ test. In addition, the neurotoxicities of these compounds were comparable to other anticonvulsant drugs.